This invention relates to electrochemical cells and methods of making electrochemical cells for detecting the presence of, measuring the amount of, and/or monitoring the level of one or more components in a liquid sample. The cells perform an electrochemical measurement by evaluating an electrochemical parameter (i.e., potential, current, resistance, etc) between two or more electrodes which are in contact with a sample. Electrode sensors typically include a working electrode and either a counter or a reference/counter (“reference”) electrode.
While use may be made of this invention in the chemical industry, especially where complex mixtures are encountered (e.g. in food chemistry or biochemical engineering) it is of particular value in biological investigation and control techniques. More particularly, it lends itself to animal or human medicine, and in particular to in vitro measuring or monitoring of components in body fluids. For convenience, the invention will be described with reference to one such procedure, the determination of glucose within a human.
In order to effectuate a measurement of glucose in a human, a sample of blood is drawn from a test subject and the sample mixed with a reagent typically comprising an enzyme and a redox mediator. The chemistry used in such a measuring device is typically:glucose+GODox--->gluconolactone+GODred GODred+2 ferricyanide--->GODox+2 ferrocyanide
where GODox is the enzyme glucose oxidase in its oxidized state, and GODred is the enzyme in a reduced state. Ferricyanide ([Fe(CN)6]3−) is the oxidized mediator which oxidizes GODred so it can oxidize further glucose molecules. Ferrocyanide ([Fe(CN)6]4−) is the reduced form of the mediator which transfers electrons to an electrode (thereby regenerating ferricyanide). Thus, the generation of ferrocyanide (measured electrochemically) indicates the concentration of glucose in the sample. Other enyzmes, such as glucose dehydrogenase, have also been used.
Because glucose monitoring for diabetics is preferably done several times a day, and because each test using conventional apparatus for home use requires a finger stick to obtain blood or interstitial fluid, the developmental pressure has been towards apparatus with ever increasing convenience to the user and lower cost. As a result, electrochemical cells with small sample test volumes have been disclosed. See, for example U.S. Pat. Nos. 6,576,101; 6,551,494; 6,129,823 and 5,437,999. As the size of the sample cell becomes smaller, however, the percentage change in electrode area and cell volume resulting from a small error in manufacturing tolerance becomes greater. This is significant because the magnitude of the signal may depend on the electrode area and cell volume. Thus, stricter manufacturing controls may be required in order to achieve the necessary precision in cell size, but these stricter controls are not compatible with the goal of reduced cost.